1,2,4-4h-triazole derivatives

ABSTRACT

Substituted 1,2,4-4H-triazoles of the formula   WHEREIN R2 is an alkyl radical or a tautomeric form thereof. These compounds are fungicides and are particularly useful for the control of cereal rusts.

Unite States Patent [191 Seidel et al.

[4 1 Feb. 18,1975

[ 1,2,4-4H-TRIAZOLE DERIVATIVES [75] Inventors: Michael C. Seidel,Levittown;

William C. Von Meyer, Willow Grove; Stanley A. Greenfield, Ambler, allof Pa.

[73] Assignee: Rohm and Haas Company,

Philadelphia, Pa.

[22] Filed: June 8, 1972 [21] Appl. No.: 263,728

Related US. Application Data [63] Continuation-impart of Ser. No.67,198, Aug. 26, 1970, abandoned, which is a continuation-in-part ofSer. No. 847,481, July 3, 1969, Pat. No. 3,701,784, which is acontinuation-in-part of Ser. No. 757,490, Sept. 4, 1968, Pat. No.3,769,411.

OTHER PUBLICATIONS Pesson, et al., Chem. Abstracts, Vol. 70, AbstractNo.

116862, (1969). QDlASl.

Pesson, et al., Chem. Abstracts, Vol. 70, Abstract No. 68323h (1969),QDA51.

Pesson, et al., C. R. Acad. Sci. Paris, Ser. C, 1968, Vol. 267, pp.904907, Q46A14.

Pesson, et al., C. R. Acad. Sci. Paris, Ser. C, 1968, Vol. 267, PP.1726-1729, Q46A14.

Primary Examiner-Alton D. Rollins [57] ABSTRACT Substituted1,2,4-4H-triazoles of the formula I Boocl -sA wherein R is an alkylradical or a tautomeric form thereof. These compounds are fungicides andare particularly useful for the control of cereal rusts.

6 Claims, N0 Drawings 1 1,2,4-4H-TRIAZOLE DERIVATIVES This applicationis a continuation-in-part of U.S. Ser. No. 67,198 filed Aug. 26, 1970,now abandoned, which in turn is a continuation-in-part of U.S. Ser. No.847,481, filed July 3, 1969, now U.S. Pat. No. 3,701,784, which in turnis a continuation-in-part of Ser. No. 757,490, filed Sept. 4, 1968, nowU.S. Pat. No. 3,769,411, Oct. 30, 1973.

This invention is concerned with substituted 1,2,4,- 4H-triazoles,hereinafter termed 1,2,4-triazoles, which possess fungicidal propertiesuseful for the control of fungal diseases on plants and in someinstances herbicidal properties and to agricultural compositionscontaining them. It also relates to certain of these 1,2,4- triazoleswhich are novel compounds and to their method of preparation. Further,it relates to certain 1,2,4-triazoles which are useful as systemicfungicides for the control of a rust disease, as on a cereal crop.

The chemistry of the 1,2,4-triazles has been reviewed by K. T. Potts inChemical Reviews 61, 87-127 (1961 A few such compounds are known topossess biological properties. 3-Amino-l,2,4-triazole is a commercialherbicide, and thiocarbamyl derivatives of it possess fungicidalproperties useful for paints according to French Pat. No. 1,425,253.Japanese Pat. Publ. 11480/66 disclosed certain 3-mercapto-4-amino-5-(substituted-methyl)-1,2,4-41-1 -triazoles as fungicides.S-Amino-1-[bis(dimethylamino)-phosphenyl]-3- phenyl-1,2,4-triazole is aknown fungicide. U.S. Pat. No. 3,308,131 discloses among others3-mercapto-1- (substituted-carbamyl)-1,2,4-triazoles useful asinsecticides.

Relatively few compounds are known to control fungal rust organisms andstill fewer which control them by systemic action. Rust fungicidesinclude symmetricaldichlorotetra-fluoroacetone,ethylenebisdithiocarbamates, nickel compounds, phenyl-hydrazones,cycloheximide and certain carboxamido oxathiins.

The substituted 1,2,4-triazoles of this invention which have been founduseful as fungicides for the control of phytopathogenic fungi arerepresented by the general formula wherein R is hydrogen or -SA whereinA is a. hydrogen,

b. alkyl groups of 1 to 12 carbon atoms and alkyl groups of l to 12carbon atoms substituted by (1) halogen, preferably chlorine, (2) loweralkoxy, (3) cyano, (4) carbamyl, (5) alkenyloxy of 3 to 6 carbon atoms,(6) phenoxy, (7) phenyl, (8) lower alkoxy, lower alkyl, halo preferablychloro or nitro substituted phenyl, (9) benzoyl and 10) halo preferablychloro, lower alkoxy, lower alkyl or nitro substituted benzoyl,

c. alkenyl of 3 to 6 carbon atoms,

d. the group -C(X)R wherein X is O or S and R is selected from the groupconsisting of lower alkyl, methoxy substituted lower alkyl, phenyl,lower alkyl substituted phenyl, lower alkoxy substituted phenyl, haloand nitro substituted phenyl, furoyl,

and the group NR R wherein R and R may be hydrogen or lower alkylgroups,

e. the group -CH(OH)R wherein R is hydrogen,

lower alkyl or lower halo-substituted alkyl,

f. the group wherein C and D are hydrogen and a meta-directing groupsuch as cyano, nitro, sulfonic acid and sulfonic acid derivatives withthe proviso that only one of C and D may be hydrogen,

g. salt-forming metals such as the alkali and alkaline earth metals,cadmium, copper, iron, manganese, nickel, tin and zinc;

R is

a. alkyl, stright or branched, of l-l8 carbon atoms which may besubstituted with hydroxy, lower alkoxy, lower-alkylamino, di(loweralkyl) amino, phenyl, methoxy-substituted phenyl, phenoxy or thiophenoxywhich may be substituted in the phenyl group with halo preferablychloro, lower alkyl,'

lower alkoxy or nitro, an imidazolyl group, :1 1,2,4- triazyl group, ora COY group wherein Y is hydroxy or lower alkoxy,

b. alkenyl of 3 to 6 carbon atoms,

c. alkynyl of 3 to 6 carbon atoms,

d. cycloalkyl of 3 to 8 carbon atoms,

e. benzyl which may be substituted in the phenyl group with lower alkyl,halo preferably chloro and nitro groups,

f. phenyl which may be substituted with halo prefera-. bly chloro, loweralkyl, lower alkoxy, cyano or nitro groups, or

g. heterocyclic group selected from the group consisting of 2-pyridyl,4-pyridyl, Z-pyrimidyl, 3-(and 4-)-l ,2,4-triazyl, l-morpholinyl,2-thiazyl, 2- benzothiazyl, 2-benzimidazolyl and their halo preferablychloro substituted derivatives; and

R is hydrogen, lower alkyl, hydroxy, furyl, and the group COOB wherein Bis hydrogen, lower alkyl, ammonium, ammonium monosubstituted with loweralkyl or lower hydroxyalkyl, ammonium disubstituted with lower alkyl orlower hydroxylalkyl, ammonium trisubstituted with lower alkyl or lowerhydroxyalkyl, quaternary ammonium and salt-forming metals; and acidsalts of the basic substituted 1,2,4-triazoles prepared from mineralacids such fluoboric, hydrobromic, hydrochloric, nitric, phosphoric andsulfuric and from mono and polybasic organic acids such as acetic,chloroacetic, acrylic, toluene-sulfonic, oxalic and maleic.

When the term lower is employed in conjunction with alkyl and alkoxy asabove it is intended to indicate that the alkyl or alkyl portion thereofhas a carbon content of 1 to 5 carbon atoms. Alkyl groups as referred tofor Formula 1 may be straight or branched chain.

Compounds of Formula 1 in which R is SH may exist in tautom eric form;thus,

g R -su m- N :8

(II) (II R lN SA r R l N or as mixtures of these. However, for thepresent purpose these compounds will be referred to as 1,2,4-4H-triazoles or more simply as 1,2,4-triazoles.

Further when R is OH two additional tautomers are possible, thus,

N SA or It is quite probable that the major component is in the lactamform; however, for the present purpose the 5- hydroxy-l ,2,4-triazoleform will be used. For a general discussion of tautomeric compounds andof the isomers that may result from synthetic procedures for producingtriazoles reference is made to Elderfield, Heterocyclic Compounds," JohnWiley, N.Y., 1957, Vol. V, pp. 9l92.

Various methods are available for the preparation of the compounds ofFormula 1.

A. For the compounds where R and R are hydrogen,

The method of Bartlett and Humphrey, J. Chem. Soc. 1967, 1,664-1,666,involving a transamination of N,N-dimethylformamide azine may be used;thus I-IiN S H (VII).

This involves reaction of hydrazine with an isothiocyanate (R NCS) toproduce a semicarbazide which is then formylated followed by cyclizationin the presence of a base catalyst; thus II NNIIe RQNCS IIeNNI-IC(S)NIIR1100011 HzNNII c s NI'IRZ I lHR This general method is described inOrganic Syntheses 40, 99 (1960) and Kroger, Sattler and Beyer, Annalen643, 128 (1961). The formation of the semi-carbazide and its formylationare standard type reactions, e.g., see Lieber, Pillai and Hites CanadianJournal of Chemistry 35, 832 (1957). These intermediates may, ifdesired, be isolated prior to the cyclization reaction. The cyclizationreaction may be conveniently carried out in the presence of a basecatalyst. Cyclization may be optimized by the use of from 2 to 3equivalents of the base catalyst. The cyclization catalyst can beselected from inorganic base catalysts such as metal hydroxides,carbonates and bicarbonates, or organic base catalysts such astriethylamine, pyridine and N,N-dimethylaniline. Sodium hydroxide is areadily available base catalyst for use in the cyclization reaction.

Since the intermediate products prior to cyclization are usually solids,a reaction solvent is usually necessary. The cyclization reaction may beconveniently carried out in any solvent medium that is inert under thereaction conditions. Suitable solvents are water, alcohols such asmethanol, butanol and propanol, benzene, hexane, or other suitable inertorganic solvents such as dimethylformamide, ether, dimethylsulfoxide,etc.

The cyclization reaction temperature is not critical. Temperatures inthe range of -10 C. to 100 C. may be used, with temperatures in therange of 25 to C. being preferred.

An alternate procedure for producing compounds of Formula Vll is toreact the intermediate semicarbazide with ethyl formate in the presenceof an alkali alkoxide,

such as sodium methoxide, and heating the mixture to produce the1,2,4-triazole; thus NaO CH3 (VIII) The cyclization of al-acyl-4-substituted thiosemicarbazide by an alkaline substance or byheat has been studied as an efficient route to compounds of Formula Vlll(Chemical Reviews 61, 99 (1961)); thus An alternate procedure involvesthe reaction of a 4- substituted thiosemicarbazide with an acid ester,e.g., the ethyl ester, in the presence of a sodium alkoxide, e.g.,sodium ethoxide; thus When in the above reaction the acid ester is acarbonate, such as ethyl carbonate, the resulting compound contains anOH group as the R substituent,

l t (IX) Compounds of Formula IX have been prepared by cyclizing1-substituted-Z-thiobiureas as described by Bradsher et a]. in theJournal of Organic Chemistry 23, 618 (1958).

D. For the compounds where R is SH and R is COOH,

HOOCAILNJ-SH This method involves reaction of a dialkyl oxalate such asdiethyl oxalate with hydazine to produce an alkyloxalyl hydrazide, whichis then reacted with an isothiocyanate (R NCS) to produce asemicarbazide, followed by cyclization in the presence of a basecatalyst such as sodium alkoxide or triethylamine. This produces thecarhoxylic ester of the Formula X compound, whichh upon acid hydrolysisgives the free acid. This may be illustrated with diethyl oxalate, thusEtOOCCOOEt H2NNH2 EtOOCC(O)NHNH2 R NCS EtOOCO(O)NHNHC(S)NHR basecatalyst l l l mooc- N SH X C. for about 30 minutes or at about 45 C.for about 4 hours. An acid catalyst often produces decarboxylation undermilder conditions. Thus, decarboxylation of compounds of Formula X isanother way of preparing compounds of Formula Vll.

E. Compounds of the type may be prepared by removal of the mercaptogroup of compounds of Formula Vlll and IX by reaction with oxidizingagents such as nitric acid or hydrogenperoxide.

F. Salts of various of the substituted 1,2,4-triazoles may be made bymethods known to one skilled in the art. Thus,

1. the basic 1,2,4-triazoles may be reacted with mineral and organicacids, e.g. see Ainsworth, et al., J. Med. Pharm. Chem. 5, 383 (1962).

2. those compounds where R is SH group may be reacted with bases such asalkali and alkaline earth hydroxides, oxides and carbonates. Of thealkali salts the sodium salt is preferred. The relatively insolubleheavy metal salts may be made by reacting a water-soluble salt of theheavy metal with a water-soluble salt of the l,2,4-triazole.

3. those compounds where R is carboxy may be reacted with metallic basessuch as alkali and alkaline earth hydroxides, oxides and carbonates;ammonia and quarternary ammonium hydroxide; and amines. For some saltssuch as quarternary ammonium and heavy metal ones it is convenient toreact a water-soluble quaternary ammonium or metal salt with awater-soluble salt of the l,2,4-triazole.

G. Derivatives of the 1,2,4-triazoles containing a 3- mercapto group,i.e., where R in Formula I is SA, may be made by methods known to oneskilled in the art. Thus:

I. where A is alkyl; alkyl substituted with various groups such asalkoxy and phenoxy; benzyl and substituted benzyl; the group -CHC(O)NR"R and the group as defined above, the compounds may be made byreaction of the respective halides with a salt of the 3-mercapto-l,2,4-triazole.

2. where A is an acyl group such as a benzoyl, furoyl group, carbamoylor thiocarbamoyl, the acyl halides may be reacted with a salt of the3-mercapto- 1,2,4-triazole.

3. where A is a lower cyanoalkyl group, the mercapto group of he1,2,4-triazole of compounds of Formula l, VII and VIII may be reactedwith an olefinic nitrile such as acrylonitrile or methacrylonitrile. Insome instances compounds of Formula V are known to result and this isparticularly true for compounds which give a Michael type addition suchas acrylonitrile, methacrylonitrile, acrylic acid, maleic acid,nitroethylene and nitrostyrene. A cyano group can also be introduced byother means known in the art such as replacement of a halo atom byreaction with a cyanide salt or by dehydration of a carbamoyl group.

4. where A is a C(O)NHR" or C(S)NHR group the mercapto 1,2,4-triazolesmay be reacted with an isocyanate (R NCO) or isothiocyanate (R NCS).

Details of preparing the compounds of this invention are given in thefollowing examples which are presented for purposes of illustration andare not intended to limit the scope of the invention. Table 1 lists bystructure and name, compounds prepared by the abovedescribed processesand constitutes Examples 1 through 130. Table 11 gives physicalcharacteristics and analyses or literature references for theseexamples. Specific illustrative preparations of Examples 1, 69, 76, 83,88, 90, 94,102,106,110,112,114,124 and 125 are set forth below.

EXAMPLE 1 Preparation of 4-n-propyl-1,2,4-triazole A reaction mixtureconsisting of g. (0.0705 mole) of N.N-dimethylformamide azine, 41.5 g.(0.705 mole) of n-propylamine, 0.6 g. of p-toluenesulfonic acid and 200ml. of benzene was refluxed 4 hrs. and then stripped of solvent. Theresidue was distilled to give 3.3 g. distilling at l20-125 C. which was4-n-propyl- 1,2,4-triazo1e.

EXAMPLE 69 Preparation of 4-(2-benzothiazy1)-1,2,4-triazole A reactionmixture consisting of 10 g. (0.0705 mole) of N,N-dimethylformamideazine, 10.6 g. (0.0705 mole) of 2-aminobenzothiazole, 0.6 g. ofp-toluenesulfonic acid and 200 ml. of dimethyl formamide was refluxed 16hrs., then stripped of solvent. The residue was recrystallized twicefrom ethanol to give 2.5 g. of solid melting at l9920l C. This was4-(2-benzothiazyl)- 1,2,4-triazole.

EXAMPLE 76 Preparation of 3-mercapto-4-n-butyl-1,2,4-triazole.

4-n-Butylthiosemicarbazide (20.0 g. or 0.136 mole) was heated to refluxwith a solution of methanol (100 ml.). sodium methoxide (7.55 g. or0.140 mole) and ethyl formate (20.7 g. or 0.280 mole). After 8 and 16hours. 10 ml. and 5 ml. of ethyl formate was added to the refluxingsolution. After 24 hours total reflux, the solvent was removed underreduced pressure and the residue was dissolved in water 100 ml. The pHof the solution was adjusted to about 12 with 50% sodium hydroxidesolution. This solution was then heated on a steam bath for 45 minutes,cooled and acidified with dilute hydrochloric acid. The resulting oilwas extracted into ether. The ether was dried over sodium sulphate andremoved under vacuum. The resulting oil was crystallized fromether-hexane to give 11.8 g. (55% yield) of3-mercapto-4-n-butyl-l,2,4-triazole, m.p. 67-69 C. The structure wasconfirmed by its nuclear magnetic resonance spectrum and its massspectrum.

EXAMPLE 83 Preparation of 3-mercapto-4-cyclohexyl-1,2,4-triazole. Formicacid (90%, 100 ml.) was heated on a steam bath for 15 minutes and then4cyclohexylthiosemicarbazide (30 g. or 0.174 mole) was addedportionwise.

The resulting clear solution was then heated for an additional 60minutes, diluted with water (50 ml.) and allowed to cool at 0 C. Aprecipitate was formed. The precipitate (13 g. or 0.065 mole) wascollected and added to a solution of sodium hydroxide (2.6 g. or 0.065mole) in water (25 ml.) and heated on a steam bath for 60 minutes. Thesolution was cooled and acidified to pH 2 with dilute hydrochloric acid.The precipitate was collected and recrystallized from ethanol to give5.3 g. of solid mp. l62165 C. The mother liquors from thecrystallization were concentrated to give an additional 4.3 g., m.p.162165 C. The total yield was 9.3 g. (78%) of 3-mercapto-4-cyclohexyl-1,2,4-triazole. The structure was confirmed by its nuclear magneticresonance spectrum and its mass spectrum.

EXAMPLE 8 8 .KOH on a steam bath for 30 min. The reaction mixture wascooled and acidified with 50% hydrochloric acid to give 25g. of crude,air-dried solid. This was recrystallized from acetone to give 18 g. ofsolid melting at 136 C. It is 3-mercapto-4-phenyl-5-hydroxy-1,2,4-triazo1e, or a tautomer thereof, containing onehalf molecule ofwater of hydration.

EXAMPLE 90 Preparation of 3-mercapto-4-methyl-5-(2-furyl)-1,2,4-triazole.

A. Preparation of 1-(2-furoyl)-4-methyl thiosemicarbazide.

Furoyl chloride (31 g. or 0.238 mole) was added dropwise to a slurry of4-methy1thiosemicarbazide (25 g. or 0.238 moles) in dry pyridine (200ml.) cooled to 10. The slurry was allowed to come to ambient temperatureand stirred overnight. The reaction mixture was poured into 1,500 ml. ofcrushed ice, the precipitate was collected, dried and recrystallizedfrom EtOH to give l-(2-furoyl)-4-methyl thiosemicarbazide (28.0 g.).This melted at 204206 C (dec.) and was found to contain by analysis42.4% C, 4.6% H, 21.2% N, 16.1% 0, 15.9% S; C H N O S requires 42.2% C,4.5% H, 21.1% N, 16.1% O,16.1% S. The structure was confirmed by itsinfrared spectrum and nuclear magnetic resonance spectrum.

B. Conversion of 1-(2-furoyl)-4-methyl thiosemicarbazide into3-mercapto-4-methy1-5-(2-furoyl)-l,2,4- triazole.

The above thiosemicarbazide (28 g. or 0.141 moles) in methanol (300 ml.)was refluxed overnight in the presence of sodium methoxide (15.2 g. or0.282 moles). The solvent was then removed under vacuum and the residuewas diluted with water ml.). The solution was then acidified withhydrochloric acid, the precipitate was collected, washed with water anddried. The solid was recrystallized from ethanol to give3-mercapto-4-methy1- 5-(2-furyl)-l,2,4-triazole melting at 192l94 C. Thestructure was confirmed by its infra-red spectrum and nuclear magneticresonance spectrum.

EXAMPLE 94 Preparation of 3-mercapto-4-n-butyl-5-carboxy-l,2,4-triazole.

A. Preparation osemicarbazide.

To a methanolic solution (200 ml.) of diethyl oxalate (100 g. or 0.683mole) was added a methanolic solution (200 ml.) of hydrazine hydrate(22.9 g. or 0.68 mole). The addition occurred over a two hour periodduring which period the reaction temperature was maintained at about C.When the addition was completed n-butyl isothiocyanate (78.4 g. or 0.68mole) was added at 5 C. The cloudy solution was stirred at ambienttemperatures for 18 hours. The reaction mixture was filtered, evaporatedunder reduced pressures to onehalf the original volume, and diluted withwater (700 ml.). The resulting precipitate was filtered and air dried togive 154.4 g. (92% yield) of lethyl oxalyl-4-n-butylthiosemicarbazide,m.p. 12728 C. It was found to contain by analysis 38.76% C, 6.23% H,19.27% N and 14.83% S; calculated for C H N O S'H O is 38.33% C, 5.98%H, 19.16% N and 14.63% S.

B. Conversion of l-ethyl oxalyl-4-n-butylthiosemicarbazide into3-mercapto-4-n-butyl-5-carboxy- 1,2,4-triazole.

The thiosemicarbazide (125.0 g. or 0.507 mole) formed above was added toa solution of sodium hydroxide (45.0 g. or 1.125 moles) in water (500ml.). After 16 hours at ambient temperature, the solution was warmed to60 C. and cooled. Dilute (37%) hydrochloric acid (112.0 g. or 1.135moles) was then added cautiously to avoid foaming. The resultingprecipitate was filtered and dried at 45 C. in a vacuum oven to give thecrude acid (96.5 g., 86% yield), m.p. 120-122 C. The acid wasrecrystallized from water (800 ml.) and dried to give essentially pure3- mercapto-4-n-butyl-5-carboxy-l,2,4-triazole (67.4 g., 61% yield),m.p. 1081 C. The structure was confirmed by its nuclear magneticresonance spectrum and infrared spectrum.

EXAM PLE 102 3-methylmercapto-4-n-butyl-1,2,4-

of l-ethyl oxalyl-4-n-butylthi- Preparation of triazole.

lodomethane (9.05 g. or 0.0637 mole) was added to a solution of 10 g. of3-mercapto-4-n-butyl-l,2,4- triazole, methanol (100 ml.), and sodiumhydroxide (2.55 g or 0.0637 mole). This solution was then refluxed for 2hours. The solvent was then removed in vacuum and the residue wasdissolved in benzene. This solution was washed with water, dried and thebenzene removed in vacuum. The residual oil was distilled to give3-methylmercapto-4-n-butyl-l,2,4-triazole, b.p. 128l 3 1 C./2 mm. Thestructure was confirmed by its nuclear magnetic resonance spectrum.

EXAMPLE 106 (yanocthylation of 3-mercapto-4-n-butyl-l ,2,4-

triazolc.

Acrylonitrile (12 g. or 0.224 mole) was added dropwise to a dioxane (30ml.) solution of 3-mercapto-4-nbutyl-l ,2,4-triazole (10 g. or 0.0638mole) in the presence of a 40% aqueous solution of benzyltrimethylam-.monium hydroxide (1 ml.). The dark red solution was left standingovernight, and the solvent was removed in vacuum. The tarry residue wastaken up in ether, washed with water, dried, and evaporated to dryness.The resulting oil was distilled to give an oil distilling at l68-l75C./2 mm. Ultraviolet spectra and the teachings of Postoviskii andShegal, Chemical Abstracts 63, 13,242, 1965 indicate this to be2-(2-cyanoethyl)-4-nbutyl-1,2,4-triazoline-3-thione.

EXAMPLE 110 Preparation of 3-( l-hydroxy-2,2.2- trichloroethylmercapto)-4-n-butyl-l ,2,4-triazole.

3-Mercapto-4-n-butyl-l,2,4-triazole (2.0 g. or 0.0127 mole) and chloral(3.68 g. or 0.0254 mole) were heated in benzene (30 ml.) until aprecipitate formed (10 minutes). The mixture was cooled, the precipitatewas collected, dried, and recrystallized from ether-hexane to give 3-(l-hydroxy-2,2,2- trichloroethylmercapto')-4-n-butyl-l,2,4-triazolemelting at -97 C. The structure was confirmed by its nuclear magneticresonance spectrum.

EXAMPLE ll2 EXAMPLE 114 Preparation of3-methylcarbamoylmercapto-4-n-butyl- 1,2,4-triazole.

To 6.0 g. (0.0382 mole) of 3-mercapto-4-n-butyl- 1,2,4-triazoledissolved in 50 ml. of ether was added 2.5 g. (0.248 mole) oftriethylamine and then -2.5 g. (0.0438 mole) of methyl isocyanate. Theresulting orange-brown solution was allowed to stand overnight.

The solid which formed was filtered and washed twice with 50 ml. ofether to give 4.7 g. (57% yield) of 3-methyl-carbamoylmercapto-4-n-butyl-l ,2,4-triazole melting at 1l2-114 C.

EXAMPLE 124 Preparation of 3-furoylmercapto-4-n-butyl-1,2,4- triazole.

3-Mercapto-4-n-butyl-l,2,4triazole (10 g. or 0.064 mole) was added to asolution of sodium hydroxide (2.6 g. or 0.064 mole) in methanol (200ml.). The solution was evaporated to dryness under reduced pressure,benzene ml.) was added, and the slurry concentrated to dryness to yieldthe sodium salt of the triazole. The salt was slurried in benzene (200ml.) and furoyl chloride (8.5 g. or 0.065 mole) was added and the slurrywas heated to reflux for 2 hours. After cooling to room temperature thebenzene was washed with water,

TABLE l-Contmued R R R Name 41... II HOOCCHzCHz H4-(2-carboxyethyl)-1,2,4-t aZ01e- 42..." II HOOCCH OHKHCB m H4-(2-carb0xyethyl)-1,2,4-t la 0l6 hydrochloride.

H aOOCHzCHz H 4-(2-methoxycarbony1ethyl)- 1,2,4-trlazole.

H HOOCCHzCHzCHz H 4-( 3 car1 oxypropyD-L2A- r azo e.

4a --H cH oocoH cn om H 4-(3-methoxy ar y p p 1,2,4-triazo1e.

H CHaOCHzCHgCHz H 4( 3- met hoxypr0pyl)- IIBZO G- H C2H5OCH2CH2CH2 H4-(3-9thoxyp1'0pyD 2. H 3)2 2CH2CH: H 4-(t3- 1soplropoxypropyl)4,2,4-

nazo e. H C5H5CH2 H 4-benzyl-1,ZA-triazole. H 4-CH OC H CH H4-(4-methoxybenzyl)4,

triazole. H 4'C1C6H4CH2 H 4-(4-ch10r0benzyl)-1.2,4-triazole. H2,4-Cl2CgH3CH2 H 4-(2,4-dichlorobenzyl)4,2,4-

triazole. H 3,4-ClzCuHaCH2 H 4-(3,4-dichlorobenzyl)-1,2,4-

triazole. H CH5. H 4-phenyl-1,2.4-triazo1e. H 3-C1CQH; (H01 salt)" H4-(3-chlorophenyl)-1,2,4-triazole hydrochloride. H 2,4- C12 0 aHa H 4-(2,4-dichlorophenyl) 4,2,4-

triazole. II 3,4-Cl2CuHa A H 4-(3,4-dichloropheny1)-1,2,4-

triazole. II 3'NO2C6H4 H 4-(3-nitrophenyl)-1,2,4-triazo1e. 11 4-N O2C5II4 H 4-(4-nitrophenyl)-1,2,4-triazole. [I 4-CII3O 06H; II4-(4-mothoxyphenyl)4,2,4-

triazolo. ll 4-pyridyl I-I 4-(4-pyridyD-l,2,4-triazo1e. II 2-pyridyl- H4-(2-pyridyl)1,ZA-triazolc. II 5-chloro-2-pyri y H4-(5-chloro-2-pyridyD-l,2,4-

- triazole. H 4-morph01inyl H 4-morpholino-1,2,4-triazole. H4-(1,2,4-triazyl) H 4-(4-(1,2,4-triazyl)-1,2,4-triazole. H3-(1,2,4-triazyl) H 4-(3-(l,2,4-t1iazyl)-1,2,4-triazo1e. H 2-pyrimidyL.H 4-(2-pyrimidyl)-1,2,4-triazole. H 2.thiaz H4-(Z-thiazyl)-1,2,4-triazole. H Z-benzothiazyl- H4-(2-benzothiazyl)-1,2,4-triazole. H 2-(4-chlorobenzoth1azyl) H4-(2-(4-c{1l0robenzothiazyl)-l,2,4-

triazo e. H Z-benzimidazolyl H 4-(2-benzimidazolyl)4,2,4-

triazole. H CH; COOCH; 3-methoxycarbonyl-4-methyl- 1,2,4-triazole. SHCH3 H 3-mercapto4-methy1-1,2,4-

triazole. SH C2H5 H 3-mercapto-4-ethyl-1,2A-triazole. SH n-C@H7 H3-mercapto4-n-propyl-l,2,4-

rriazole SH n-C4Hn H 3-mercapto-4-n-butyl-1,2,4-

triazole. SH t-O4Hv H S-mercapto-4-t-butyl-1,2,4-

trlazole. SII n-C5H11 H 3-mercapto-4-n-pentyl-l,2,4-

triazole. SH 1L-COH1z H 3-mercapto-4-n-hexyl-1,2,4-

triazole.

9.11 71-0311" H 3-mercapto-4-n-octyI-1,2,4-

tfluzole. RH t-CuIIn II 3-mercaPto-4-t-octyl-l,2,4-

Z0 0. s11 'Il-C]n]I2l II 33-11] nrcapt0-4-n-dccyl-l,2,4-

triuzolc.

83 .7 SH Cyclohexyl II 3-mercapto-4-cyclohcxyl-I,2,4-

trinzolo g4 s11 (M1 011; H 3-mercapt04-benzyl-1,2,4-

triazole 35 SH Phenyl H 3-mercapto4-pheny1-1,2,4-

triazole.

86", SH CH: OH 3-mercapto4-methy1-5-hydroxy- 1,2.4-triazole.

87 SH C4Ha 0H 3-mercapt0-4'n-butyl-S-hydroxy- 1,2,4-triazole.

88 SH Cal-I5 0H 3-mercapto-4-phenyl-5-hydroxy- 1,2,4-triazo1e.

89". SH C4Hg CH S-mercapto-4-n-butyl-5-methyl- 1,2.4-triazole.

90..-.. SH CH3 3-mercapto-4-methyl-5-(2-fuxyl)- 1,2,4-triazole.

91.... SH C4H 3-mercapto-4-n-butyl-5-(Z-furyl)- 1,2,4-triazole.

92. SH Phenyl 3-mercapto-4-phenyl-5-(2fury1)- 1,2.4-triazole.

93.. SH CH3 GOOH 3-mercapto-4-methyl-5-carboxy- 1,2,4-triaz01e.

94.... SH C'4H COOH 3-mereaptoi-n-butyl-fi-carboxy- 1,2.4-triaz0le.

95..... SH 04m COOH-(HOCHGH2)3N triethanolamine salt of3-mercapto-4-n-butyl-5-carboxy- 1,2,4-Lriaz01e.

9 1 CH COOCH B-mercapto-4-methyl-5-methoxycarbonyl-1,2,4-mazole.

7- H C4119..- COOCZH a-mercapto-4-n-butyl-5-ethoxycarbonyl1,2,4-tr1azole.

" 04H 0000 11 Sodium salt of 3-mercapt0-4- buLyl-fi-ethoxycnrbonyl-l,2,4Lriumlc.

* (0)N l ll;; m 00ml 3-mnLhykmrhmnoylnmrcnpto-4- TABLE lI-CntinuedCharacterization of Examples Example Melting Empirical Analysis orLiterature Reference No. Point (C.) Formula C H N g S 100 concentrate Cm- 19 0 8 50.0 (50.6) 9.5 (8.1) 20.9 (19.5) 7.8 (8.9) 101 brown oil 102128-131/2 mm." C,H, -,N S 49.1 (49.1) 7.6 (7.6) 24.6 (24.6) 19.0 (18.7)103 140-155/.5 mm." C H N s 56.1 (56.2) 8.9 (9.0) 20.2 (19.7) 15.1(15.2) 104 195-205/.1 mm." C H N S 64.7 (64.7) 10.7 (10.5) 14.5 (14.1)10.6 (10.8) 105 136-152/.06 mm." C,,H; N ,S 54.3 (54.8) 8.0 (7.7) 21.3(21.3) 16.4 (16.2) 106 168-175/2 mm." C,,H N,S 51.2 (51.4) 6.8 (6.7)26.65 (26.7) 15.1 (15.2) 107 147-155/1 mm." C HQN OS 52.7 (52.3) 8.2(8.3) 18.8 (18.4 14.45 (14.0) 108 160-170/.05 mm." C H N OS 52.8 (52.9)7.7 (7.5) 18.5 (18.5) 14.1 (14.1) 109 220-230/ mrn. C,,H,,,N OS 60.9(60.6) 7.3 (6.9) 15.05 (15.2) 10.9 (11.5) 110 -97 C,,H, c1 N.-,os 31.8(31.6) 4.2 (3.95) 13.95 (13.8) 10.8 (10.5) 111 74-76 C H N OS 45.6(44.8) 6.3 (6.5) 26.7 (26.2) 14.3 (15.0) 112 190-205/.03 mm. C H N- 0S60.6 (60.6) 7.1 (6.9) 16.0 (15.2) 10.95 (11.5) 113 -107 C H, N O,S 44.8(44.6) 4.3 (4.0) 21.5 (21.7) 20.1 (19.8) 114 112-114 C,,H N OS 45.1(44.9) 6.7 (6.6) 26.2 (26.2) 14.8 (14.9) 115 123-126 C H N OS 48.1(48.3) 6.4 (6.6) 21.0 (21.0) 16.1 (16.1) 116 118-120 C,,H ,N O S ,47.2(47.2) 6.3 (6.6) 18.3 (18.3) 12.6 (14.1) 117 109-112 C...H..N..os 5351:,(52.9) 7.4 (7.5) 18.8 (18.7) 12.6 (14.1) 118 143-144 C H BrN OS 46.2(45.9) 4.05 (14.1) 12.4 (12.3) 9.5 (9.4) 119 160-162 C H BrN 0S I 45.8(45.9) 4.0 (4.1) 12.2 (12.3) 9.5 (9.4) 120 154-156 cmHuclgNgos 48.2(47.4) 4.0 (3.9) 12.7 (12.7) 9.7 (9.7) 121 94-96 C H N O S 57.7 (57.7)5.8 (5.9) 14.4 (14.4) 11.0 (11.0) 122 114-116 C H N O S 51.0 (51.0) 5.2(4.6) 18.3 (18.3) 10.5 (10.4) 123 162-165 C ;H ,N O S 54.3 (54.7) 5.9(6.0) 11.7 (11.9) 9.1 (9.1) 124 102-5 C H N O S 52.7 (52.6) 5.5 (5.2)16.6 (16.7) 12.7 (12.8) 125 79-82 C H N o S 58.1 (59.1) 6.4 (6.3) 13.6(13.8) 10.4 (10.5) 126 100-102 Chemical Abstracts 63, 13242 (1965) 127105-107 C, H, N O S 44.8 (44.6) 4.3 (4.0) 21.5 (21.7) 10.0 (9.9) 128248-250 C H,,N O,S 49.0 (49.0) 2.8 (2.6) 20.3 (20.4) 9.4 (9.3) 129174-176 01.11.114.025 61.9 (61.8) 4.25 (4.2) 13.5 (13.5) 10.5 (10.3) 130143-146 C H N O S 55.35 (55.2) 3.25 (3.1) 17.2 (17.2) 9.9 (9.8)

The number in parenthesis represents the theoretical value as calculatedfrom the empirical formula llniliug point in "C. MS mass spcc1ra and NMRNuclear Magnetic Resonance.

Among the structures ofthis invention which are fungicidal the preferredcompounds are those which are novel. Novel structures within thisinvention may be represented by the structure phenyl, (8) lower alkoxy,lower alkyl, halo prefera- 55 bly chloro or nitro substituted phenyl,(9) benzoyl and (10) halo preferably chloro, lower alkoxy, lower alkylor nitro substituted benzoyl,

c. alkenyl of 3 to 6 carbon atoms,

d. the group -C(X)R wherein X is O or S and R 60 is selected from thegroup consisting of lower alkyl, methoxy substituted lower alkyl,phenyl, lower alkyl substituted phenyl, lower alkoxy substituted phenyl,halo and nitro substituted phenyl, furoyl,

and the --NR"R wherein R and R may be hydro- 65 gen or lower alkylgroups,

e. the group CH(OH)R wherein R is hydrogen,

lower alkyl or lower halo-substituted alkyl,

whrerein C and D are hydrogen and a metadirecting group such as cyano,nitro, sulfonic acid and sulfonic acid derivatives with the proviso thatonly one of C and D may be hydrogen,

g. salt-forming metals such as the alkali and alkaline earth metals,cadmium, copper, iron, manganese, nickel and zinc;

When A is hydrogen R is alkyl of 3-18 carbon atoms which may besubstituted with one or more halo preferably chloro, lower alkoxy,hydroxy or nitro groups; and cycloalkyl of 3-8 carbon atoms which may besubstituted with one or more halo preferably chloro, hydroxy or nitrogroups;

When A is methyl R is alkyl of 3-18 carbon atoms which may besubstituted with one or more halo preferably chloro, lower alkoxy,hydroxy or nitro groups; benzyl and benzyl in which the phenyl group issubstituted with lower alkyl, halo preferably chloro and nitro groups;

When A is carbamoylmethyl, benzyl, nitrobenzyl or sodium R is alkyl ofl-l8 carbon atoms which may be substituted with one or more halopreferably chloro, lower alkoxy, hydroxy or nitro groups; benzyl andbenzyl in which the phenyl group is substituted with lower alkyl, halopreferably chloro and nitro groups;

When A is all other values R is alkyl of 1-1 8 carbon atoms which may besubstituted with one or more halo preferably chloro, lower alkoxy,hydroxy or nitro groups; cycloalkyl of 3-8 carbon atoms which may besubstituted with one or more halo preferably chloro, hydroxy or nitrogroups; benzyl, benzyl substituted in the phenyl group with lower alkyl,halo preferably chloro, and nitro groups; phenyl and lower alkyl, halopreferably chloro, and nitro substituted phenyl; and

R is hydrogen, lower alkyl, furyl and the group COOB wherein B ishydrogen, lower alkyl, ammonium, ammonium monosubstituted with loweralkyl or lower hydroxyalkyl, ammonium disubstituted with lower alkyl orlower hydroxyalkyl, ammonium trisubstituted with lower alkyl or lowerhydroxyalkyl, quaternary ammonium and salt-forming metals; and acidsalts of the compounds of Formula Xll which are basic.

Other novel structures within the scope of this invention and which arepreferred fungicides may be depicted by the formula XX I wherein R is a.alkyl, straight or branched, of 3 to 18 carbon atoms, exclusive ofn-butyl, which may be substituted with hydroxy, lower alkoxy, loweralkylamino, di(lower alkyl) amino, phenyl, methoxysubstituted phenyl,and imidazoyl group, a 1,2,4- triazyl group or a COY group whereinn Y ishydroxy or lower alkoxy, b. alkenyl of 3 to 6 carbon atoms, 0. alkynylof 3 to 6 carbon atoms, d. cycloalkyl of 2 to 8 carbon atoms, and e. aheterocyclic group selected from the group consisting of Z-thiazyl,Z-pyrimidyl, morpholino, 2- benzothiazyl, and their chlorinatedderivatives and chlorinated Z-pyridyl. Other novel structures within thescope of this invention may be depicted by the formula HO-LJ SH MAKE XI22 3-mercapto-4-(4-chlorobutyl)-l ,2,4-triazole3-mercapto-4-(4-methoxypropyl l ,2,4-triazole 13-mercapto-4-(2-hydroxylbutyl)-l ,2,4-triazole 3-mercapto-4-(4-nitrobutyl l ,2,4-triazole 3mercapto-4-cyclopropyl-1,2,4-triazole3-methylmercapto-4-( 3-chloropropyl l ,2.4-triazole3-ethylmercapt0-4butyl-l ,2,4-triazole 3-butylmercapto-4-(2-chloropropyl )-i ,2,4-triazole 3-chloromethylmercapto-4butyl-l,2,4-triazole 3-( 2-hydroxyethylmercapto )-4-butyll ,2,4-triazole 3-(Z-cyanoethylmercapto )-4-butyl-l ,2,4-triazole3-(2-nitroethylmercapto)-4-butyl-l ,2,4-triazole 3-[2-(4-chlorophenoxy)ethylmercaptol-4-butyll,2,4-triazole3-[2-(Z-methylphenoxy)ethylmercapto1-4-butyll ,2,4-triazole 3-[2-( 3nitrophenoxy )ethylmercapto1-4-butyll ,2 ,4-

triazole 3-benzylmercapto-4 butyll ,2,4-triazole3-(4-chlorobenzylmercapto )-4-buty|- l ,2,4-triazole3-(dodecylbenzylmercapt0 )-4-butyl-l ,2,4-triazole3phenacylmercapto-4-butyl-1,2,4-triazole3-(3,5-dichlorophenacylmercapto)-4-butyl-1,2,4-

triazole 3-benzoylmercapto-4chloropropyl-l ,2,4-triazole3-(3nitrobenzoylmercapto)-4-benzyl-l ,2,4-triazole3carbamoylmercapto-4-benzyl-l ,2,4-triazole3-methylcarbamoylmercapto-4-(4-chlorobenzyl 1,2,4-triazole3dimethylcarbamoylmercapto-4-(2-chloroethyl)- 1,2,4-triazole3-carbamoylmethylmercapto-4-( 3-chloropropyl 1,2,4-triazole3-carbamoylmethylmercapto-4-( 2-methoxybenzyl)- 1,2,4-triazole3-carbamoylmethylmercapto-4-(4-nitrobenzyl 1,2,4-triazole3-methylcarbamoylmethylmercapto-4-butyl-l ,2,4-

triazole 3hydroxymethylmercapto-4-(2-chlo'robutyl)-1,2,4-

triazole 3chloromethylmercapto-4-butyl-l ,2,4-triazole 3-(l-hydroxy-2,4-dichloroethylmercapto)-4-(2- chloropropyl)-l ,2,4-triazole3-(2-nitrophenylmerc apto )-4-( 3-bromopropyl l,2,4-triazole3-(2-cyanophenylmercapto)-4-butyl-l ,2,4-triazole3-(4-sulfonamidophenylmercapto)-4-benzyl-l ,2,4-

triazole 3-(4-nitrophenylmercapto)-4-(4-chlorobenzyl)- 1,2,4-triazole3-furoylmercapto-4-( 3-chloropropyl)-l ,2,4-triazole3-furoylmercapto-4-( 2-chlorobenzyl)-1 ,2,4-triazole 3-mercapto-4-(2-chloroethyl )-5-methyl-l ,2,4-

triazole 3-mercapto-4-(2-chlorobenzyl)-5-furyl-l ,2,4-

triazole 3-mercapto-4-(4-chlorobutyl)-5-butyl-1,2,4-triazole 3-mercapto-4-( 2-bromopropyl )-5-( 2-hydroxyethyl)- 1,2,4-triazole3-mercapto-4-benzyl-5-( Z-nitroethyl )-l ,2,4-triazole3-mercapto-4-cyclopentyl-S-hydroxymethyl-l ,2,4-

triazole 3methylmercapto-4-butyl-S-methyl-l ,2,4-triazole3-ethylmercapto-4-( 3 chloropropyl )-5- chloromethyl-l ,2,4-triaz0le 233-(2-chloroethylmercapto)-4-(2-chloroethyl)-5- carboxy-l ,2,4-triazole3-carbamoylmercapto-4-(3-methoxypropyl)-5- carboxy-l ,2,4-triazole3-(3-methoxypropylmercapto)-4-(4-chlorobenzyl)- S-carboxy-l,2,4-triazole 3-(4-nitrophenylmercapto)-4-(3-bromopropyl)-5- carboxy-l,2,4-triazole 3-(4-methylbenzoylmercapto)-4-octyl-5-hydroxy-1,2,4-triazole 3-mercapto-4-(Z-hydroxyethyl)-5-hydroxyl ,2,4-

triazole 3-mercapto-4-(2-chlorobutyl)-5-hydroxy-l ,2,4-

triazole The l,2,4-triazoles of this invention and salts thereof possessbiocidal properties and in this respect are particularly useful asagricultural fungicides. As such, they may be applied to various locisuch as the seed, the soil or the foliage. For such purposes the1,2,4-triazoles may be used in the technical or pure form as prepared,as solutions or as formulations. The compounds are usually taken up in acarrier or are formulated so as to render them suitable for subsequentdissemination as pesticides. For example, the 1,2,4-triazoles may beformulated as wettable powders, emulsifiable concentrates, dusts,granular formulations, aerosols, flowable emulsion concentrates. In suchformulations, the compounds are extended with a liquid or solid carrierand, when desired, suitable surfactants are incorporated.

It is usually desirable, particularly in the case of foliar sprayformulations, to include adjuvants, such as wetting agents, spreadingagents, dispersing agents, stickers, adhesives and the like inaccordance with agricultural practices. Such adjuvants commonly used inthe art may be found in the John W. McCutcheon, Inc. publicationDetergents and Emulsifiers 1967 Annual. Of course the surfactant shouldbe selected rela tive to the specific triazole. In some instances thecationic l,2,4-triazole salts may be incompatible with anionicsurfactants and the anionic 1,2,4-triazole salts may be incompatiblewith cationic surfactants.

In case the 1,2,4-triazole compound is water-soluble, it may bedissolved directly in water to provide an aqueous solution forapplication. Similarly, the compounds of this invention may be dissolvedin a watermiscible liquid, such as methanol, ethanol, isopropanol,acetone, dimethylformamide or dimethyl sulfoxide or mixtures of thesewith water and such solutions extended with water. The concentration ofthe solution may vary from 2% to 98% with a preferred range being 25% to75%.

For the preparation of emulsifiable concentrates, the compound may bedissolved in organic solvents, such as xylene, pine oilorthodichl'orobenzene, methyl oleate, or a mixture of solvents, togetherwith an emulsifying agent which permits dispersion of the pesticide inwater. The concentration of the active ingredient in emulsionconcentrates is usually to and in flowable emulsion concentrates, thismay be as high as 75% Wettable powders suitable for spraying, may beprepared by admixing the compound with a finely divided solid, such asclays, inorganic silicates and carbonates, and silicas and incorporatingwetting agents, sticking agents, and/or dispersing agents in suchmixtures. The

concentration of active ingredients in such formula- 1 24 tions isusually in the range of 20% to 98%, preferably 40% to Dusts are preparedby mixing the 1,2,4-triazoles with finely divided inert solids which maybe organic or inorganic in nature. Materials useful for this purposeinclude botanical flours, silicas, silicates, carbonates and clays. Oneconvenient method of preparing a dust is to dilute a wettable powderwith a finely divided carrier. Dust concentrates containing 20% to ofthe active ingredient are commonly made and are subsequently diluted to1% to 10% use concentration.

The 1,2,4-triazoles can be applied as fungicidal sprays by methodscommonly employed, such as conventional high-gallonage hydraulic sprays,low gallonage sprays, airblast spray, aerial sprays and dusts. Thedilution and rate of application will depend upon the type of equipmentemployed, the method of application and diseases to be controlled, butthe amount is usually 0.1 lb. to 25 lbs. per acre of the activeingredient.

As a seed treatment, the amount of toxicant coated on the seed isusually at a dosage rate of about 0.1 to 20 ounces per hundred pounds ofseed. As a soil fungicide the chemical may be incorporated in the soilor applied to the surface usually at a rate of 0.1 to 25 lbs. per acre.As a foliar fungicide the toxicant is usually applied to growing plantsat a rate of 0.25 to 10 pounds per acre.

The substituted 1,2,4triazoles of this invention are also of interestwhen mixed with fertilizers and fertilizing materials. Such mixtureswith fertilizers may be made in a variety of ways. For example, liquidformulations may be sprayed onto particles of mixed fertilizer or offertilizer ingredients, such as ammonium sulfate, ammonium nitrate,ammonium phosphate, potassium chloride or sulfate, calcium phosphate orurea, singly or in admixture. Also, the toxicants and the solidfertilizing materials may be admixed in mixing or blending equipment.Similarly, a solution of toxicants in a volatile solvent may be appliedto particles of fertilizer or fertilizer ingredients. A particularlyuseful form in which the toxicants are incorporated with fertilizers isin granular formulations. This type of solid composition serves a dualpurpose in providing fertilizing material for the rapid growth ofdesired plants and at the same time helps control fungal diseases in oneoperation without the necessity of separate applications.

The compounds of this invention were evaluated as foliar fungicides forthe control of wheat leaf rust, Puccinia recondita. In this test aqueoussprays were applied to about one week old wheat seedlings and the plantswere allowed to dry. They were then inoculated with standard sporesuspension of the wheat leaf rust organism containing approximately25,000 spores per ml. The plants were then held under standardconditions for the disease to develop. After about 7-9 days, lesionswere counted and compared to those on untreated plants. The percentdisease control was calculated. In a related test in order to determinethe persistency of the sprays, the treated plants were rained upon forvarying times in a standard rain machine in which 6 minutes of rain wasequal to about 1 inch of rain. Table III gives the results. Dashesindicate no data.

Table lll Table Ill-Continued Wheat Leaf Rust Control by FoliarAppliation Wheat Leaf Rust Control by Foliar Appliation 7r Control 7:Control 5 Control Control Example (without rain) (with l" of rain)Example (Wlthout a ith l" of am) 1 1b. 0.25 lb. 1 1b. 0.25 lb. No. 1 lb.0.25 lb. 1 1b. 0.25 lb.

98 100 86 100 100 l 100 100 100 87 99 99 99 100 100 Z 90 0 40 100 100100 100 100 3 100 I00 100 101 100 100 100 100 4 95 95 60 102 100 100 5151 5 99 97 69 78 103 90 50 80 50 6 100 100 95 95 104 98 80 98 45 7 100100 100 100 105 95 50 9 5 8 99 98 100 98 106 100 100 100 99 2 :88 2% 22107 100 100 100 100 108 85 35 40 25 13 60 20 30 0 15 109 100 100 100 9614 100 100 100 99 110 100 100 100 100 12 108 108 108 93 111 100 100 10093 1 112 100 100 97 98 17 5 60 0 0 113 100 100 100 98 18 0 0 0 0 114 100100 100 100 19 65 65 0 0 115 100 99 95 90 20 0 0 0 0 20 116 100 100 9995 21 10 10 0 0 117 100 100 99 95 22 90 90 0 0 118 100 100 100 100 24 9580 95 50 119 100 100 100 100 25 0 0 0 0 120 100 100 98 98 26 10 0 0 0121 98 90 .100 100 29 20 0 0 0 l22 100 100 100 I00 30 95 90 75 25 123100 98 98 90 31 98 95 60 124 100 100 100 100 32 99 95 85 30 125 60 30 2033 100 100 126 96 93 96 83 34 35 15 15 15 127 100 99 95 3 40 30 10 (1128 100 I00 90 84 36 m 0 10 0 129 100 100 99 100 37 0 0 0 5 30 130 10097 40 40 40 10 10 41 90 85 0 0 22 58 10(5) 33 Other tests in which thespray residue was allowed to 47 80 80 55 30 age for several days beforebeing rained upon demon- 33 8 8 8 35 strated excellent persistency. 50100 100 The compounds of this invention which have exhibg8 8 $3 itedexcellent systemic activity in the control of cereal g 90 5 25 rusts areof the structure 55 100 100 56 65 90 5 57 90 60 4o 4 N--N 5s 80 80 0 0 II 59 98 97 79 58 60 100 100 97 93 N 61 10 10 0 6 100 100 99 (XV) 63 9590 45 4 64 94 88 5 65 78 64 whereln R 1s hydrogen or the group -SAwherein A 15 2; 3 82 99 hydrogen, cyano-substituted lower alkyl, loweralkoxy 68 73 66 96 67 substituted lower alkyl, the group Cl-l(OH)CCl 69100 100 98 3g Cl-l C(O)NR R wherein R and R are hydrogen or Z? 8 38 l 050 lower alkyl, benzyl, methoxybenzyl, the group 73 50 34 10 0 C(X)NR Rwherein X is O or S and R and R are g; 88 3? g 8 hydrogen or loweralkyl, methoxybenzoyl, furoyl, 2,4- 76 100 100 100 100 dinitrophenyl andsalt-forming metals; R is alkyl of 3 77 100 68 80 to 6 carbon atomsexclusive of the tert-butyl group, 33 :88 3 {88 100 55 lower alkoxyalkyl and benzyl; and R is hydrogen or 80 100 100 65 51 the -COOB groupwherein B is hydrogen, lower alkyl g; 22 2 2; 22 or a metal, ammonium,amine or quaternary ammo- 3 34 44 93 100 nium salt-forming group. 8 100gg 88 The preferred compounds are those in which R" is g2 g3 96 63 63 60a n-butyl group, e.g. 4-n-butyl-1,2,4-triazole, 3- 87 49 15 0 omercapto-4-n-butyl-1,2,4-triazole and 3-mercapto-4-n- :3 2: hutyl-S-carboxyl ,2.4-triazole. 28 0 87 811 As one test for systemic activity thecompounds were 73 8 evaluated by a root-uptake method. ln theroot-uptake 35 0 0 65 test one of the active compounds of thisinvention, con- 94 100 83 82 tained in a suitable formulation, wasincorporated into 32 3g 38 10(5) the soil by either spraying it into arotating drum of soil,

0 97 100 100 100 100 or by drenchlng the soll. The dosage of actlvemgredlent in the soil ranged from about 50.0 to about 2.5 parts permillion (ppm). Seeds of a susceptible wheat variety were planted in thetreated soil and allowed to germinate and grow to a height of about 4inches. The

Table V Foliar Systemic Activity on Leaf Rust plants were theninoculated with a spore suspension of 5 j Puccinia recondita. The plantssprayed with sportes of Sprayed Leaf New growth the rust fungus werethen held at 70 F. in a moist f :6? g f ds (3 g chamber about 16 hoursto permit infection. The lesions were allowed to develop about one weekand 3 99 96 97 100 g3 5 were then counted in comparison to untreatedplants 10 49 99 76 42 87 54 76 97 88 80 90 77 75 and the percent diseasecontrol calculated. Table IV 78 98 96 91 92 79 57 gives the results.Dashes indicate no data. 79 96 88 85 65 4s 38 TABLE IV Systemic Activityby Root'Uptake 7: Systemic Wheat Leaf Rust Control ppm in soil ExampleNo. R R" R' 10 5 2.5

1 H C;,H H 100 99 3 H n-C H H 100 100 r00 4 H i-crHg H 100 8 H i-C H H100 9 H CQHl H 92 77 46 H CH OCH CH CH H 99 96 49 H CGHSCHZ H 99 9s 9657 H 3.4-Cl C H H 68 54 63 H 5-chloro-2-pyridyl H 95 75 SH C H H 84 8276 SH C,H,, H 100 97 83 73 -sH CSHH H 97 97 97 79 SH C..H H 54 0 0 84-SH C.;H5CH2 H 64 34 0 94 'SH L1H COOH 100 99 95 95 -SH C H COONH(CH2C-100 99 98 H2OH)" 97 SH H CO0C2H5 109 95 93 9x s19 04H, COOC2H5 99 97 x599 S((())NH(H;, th, COOH 100 99 96 11111 S('(())NH(H;, (".H(.OONH((.H2L- 99 99 x9 H20H). 1111 -S((S)N1('H=,)- (,H,. cooH 100 96 xxI06 12-(Z-cyanocthyll-4-n-butyl-l1.4-triazolinc-B-thionc) 92 X6 X2 107-SCH2CH?OC,H;, (1H,. H 89 x5 52 1111 -SCH(OH )CCl C.H H 100 100 9a 111-scH C(0)NH C H. H 92 9.1 76 112 -SCH2C';H4OCH-4 H, H 72 71 64 113-SC.;H;,(NO2)2-2,4 (1H, H 100 94 67 114 -sC(o)NHcH H H 100 100 96 121-sC(0)C H. OCH -4 C ,H9 H 100 100 98 124 -S-furoyl 4H,, H 99 99 94 125-SCH2COC6H4OCH3-4 C4H9 H 44 68 55 Another type of systemic test was runin which pots 84 78 63 54 54 34 36 of approximately 5 inch high wheatplants were sprayed 3; 3g 3% L 38 2' with varying concentrations of thetest compound. 97 86 73 31 54 75 7 99 69 74 81 82 69 56 100 79 79 57 7963 54 Thirty-six hours later they were sprayed 6 minutes in a 2 3 3 rainmachine which amounted to about 1 inch of nor- 113 98 93 81 81 69 57 malrainfall. The plants were then placed in a greeng? 8? 3g 2; house for 7days and then inoculated with a spore sus- 126 0 0 42 27 0 pens1on ofwheat leaf rust, Puccinia recondita. About 7 Pluntvflx 49 37 3 38 32days later lesion counts were made on ten leaves representing thesprayed leaves and new growth from each A field test was conducted-inwhich 3-mercapto-4'nreplicate and compared with similar pots of wheatbutyl-l,2,4-triazole (the compound of Example 76), plants which wereuntreated with a chemical and the Plantvax and maneb (manganeseethylenebisdithiocarpercent control determined. Disease control on thebamate) were evaluated for the control of leaf rust on new growth is ameasure of systemic activity. The comwinter wheat planted in September.Applications of the mercial product known by the trademarked namechemicals were made the following April when the Plantvax. which is2,3-dihydro-5-carboxanilido-6- wheat was 16-24 inches tall and in theboot stage. The methyl-l ,4-oxathiin-4,4,-dioxide, was used as astanvolume of spray was 40 gallons per acre. Forty-six days dard. TableV gives the results.

after application lesion counts were made of 200 leaves per plot forfour replications and compared with check (untreated) plots. This givesa measure of systemic control. Table VI gives the results.

Table VI Systemic Field Test Treatment lbs/acre No, of lesions/800leaves Example 76 2 89 0.5 453 Plantvax 2 690 0.5 l l 13 Untreated 1 I09Table VII Systemic Field Test Treatment lbs/ acre Leaves infectedExample 76 Example 94 Plantvax Representative compounds of thisinvention have given good control olvarious fungal organisms. Forexample, compounds of the type R Lscoomum R: (XVI) wherein R is loweralkyl, R is hydrogen and carboxy and its triethanol amine salts, R and Rare hydrogen or lower alkyl, and X is O or S have given 80% or betterkills of Plzylophthora infestans at 1,200 ppm. Compounds of Formula XIIIwherein R is alkyl or alkyl substituted with hydroxy, alkoxy or aryloxy,e.g., Examples I0, 18, 24, 25 and 47, have given good control ofPllytophtlzora infestans by foliar application at 1,200 ppm or by rootuptake from treated soil containing ppm. Example 13,4-n-dodecyl-l,2,4-triazole, gave 95-lO0% control of rice blast,Piricularia oryzae, by foliar application at 1,200 ppm. Example 112,3-(4- methoxybenzylmercapto)-4-butyl-l,2,4-triazole, gave 50-85% controlof Bolryris cinerea on broad beam at 1,200 ppm. When beets were grown ina soil containing 200 ppm of Example l2],3-(4-mcthoxyhenzoylmercapto)-4-butyl-l,2,4-triazole, an excellentcontrol of Pyllu'um ullimum was obtained.

The compounds of this invention may be utilized as the sole biocidalagents, alone or in admixture, or they may be employed in conjunctionwith other fungicides or with insecticides, miticides, bird repellentsand comparable pesticides.

Fungicides which may be combined with the 1,2,4 triazoles of thisinvention include dithiocarbamates and derivatives such as ferricdimethyldithiocarbamate (ferbam), zinc dimethyldithiocarbamate (ziram),manganese ethylenebisdithiocarbamate (maneb) and its coordinationproduct with zinc ion, zinc ethylenebisdithiocarbamate (zineb),tetramethylthiuram disulfide (thiram) and 3,4-dimethyll,3.5ZH-tetrahydrothiadiazine- 2-thione; nitrophenol derivatives such asdinitro-( lmethylheptyl)phenyl crotonate (dinocap), 2-sec-butyl-4,6-dinitrophenyl 3,3-dimethylacrylate (binapacryl) and2-sec-butyl-4,6-dinitrophenyl isopropyl carbonate, heterocyclicstructures such as N- trichloromethylthiotetrahydro-phthalimide(captan), N-trichloromethylthiophthalimide (folpet),2-heptadecyl-2-imidazoline (glyodin),2,4-dichloro-6-(ochloroanilino)-s-triazine, diethylphthalimidophosphorothioate, [bis(dimethylamino)phosphinyl]-3-phenyl-l,2,4- triazole, 5.-ethoxy-3-trichloromethyl-1,2,4-thiadiazole,

2,3-dicyanol ,4-dithiaanthraquinone (dithianon 2-thio-l,3-dithio-[4,5-b]quinoxaline (thioquinox), 1-(butylcarbamoyl)-2-benzimidazole carbamic acid methyl ester,4-(2-chlorophenylhydrazone)-3-methyl- S-isoxazolone,pyridine-Z-thioll-oxide, 8- hydroxyquinoline,2,3-dihydro-5-carboxanilido-6- methyl-l,4-oxathinin-4,4-dioxide, andbis(p-chlorophenyl)-3-pyridinemethanol; and miscellaneous fungicidessuch as dodecylguanidine acetate (dodine), 3-[2-(3,S-dimethyl-2-oxycyclohexyl)-2-hydroxyethyllglutarimide(cycloheximide), phenylmercuric acetate, N-ethylmercuri-l,2,3,6-tetrahydro-3,o-endomethano- 3,4,5,6,7,7-hexachlorophthalimide,phenylmercuric monoethanolammonium lactate, 2,3-dichloro-l,4naphthoquinone, l,4-dichloro-2,4-dimethoxybenzene,p-dimethylaminobenzenediazo sodium sulfonate, 2-chlorol -nitropropane,polychloronitrobenzenes such as pentachloronitrobenzene, methylisothiocycanate, fungicidal antibiotics such as griseofulvin orkasugamycin, tetrafluorodichloroacetone, l-phenylthiosemicarbazide,Bordeaux mixture, nickel-containing compounds and sulfur.

We claim: 1. A compound of the formula BOOClN SA hydrogen, alkyl of 1 toS carbon atoms, an alkali metal ion, ammonium monosubstituted with loweralkyl or lower hydroxyalkyl, ammonium disubstituted with lower alkyl orlower hydroxyalkyl or ammonium trisubstituted with lower alkyl or lowerhydroxyalkyl.

2. A compound of the formula 5-amino-lwherein R is alkyl, straight orbranched, of l to 12 carbon atoms; A is the C(O)NHCH group; and B ishydrogen, alkyl of l to 5 carbon atoms, an alkali metal ion, ammoniummonosubstituted with lower alkyl or lower hydroxyalkyl, ammoniumdisubstituted with lower alkyl or lower hydroxyalkyl or ammoniumtrisubstituted with lower alkyl or lower hydroxyalkyl.

3. A compound of the formula l l noocl SA 3-mercapto-4-n-butyl-5 UNITEDSTATES PATENT OFFICE CERTIFICATE OF CORREQ'HQN Patent No. 3,867,395Dated February 18, 1975 Inventor(s)MiCh8.el C. Seidel, William C. VonMeyer,

Stanley A. Greenfield It is certified that error appears in theabove-identified patent and that said Letters Patent are herebycorrected as shown below:

Column 2, line 20, "stright" should read --straight--.

Claim 1, column 30, line 55 is omitted. It should read --wherein R isbutyl; A is hydrogen; and B is--.

Signed and sealed this 6th day of May 1975.

(SEAL) Attest:

C. MARSHALL DANN RUTH C. MASON Commissioner of Patents Attesting Officerand Trademarks

1. A COMPOUND OF THE FORMULA
 2. A COMPOUND OF THE FORMULA
 3. A COMPOUNDOF THE FORMULA
 4. The compound3-mercapto-4-n-butyl-5-carboxy-1,2,4-triazole.
 5. The compound3-mercapto-4-n-butyl-5-ethoxycarbonyl-1,2,4-triazole.
 6. Thetriethanolamine salt of3-methylcarbamoylmercapto-4-n-butyl-5-carboxy-1,2,4-triazole.